ETH Zurich, Department of Materials, Zurich, Switzerland.
Tissue Eng Part B Rev. 2012 Jun;18(3):181-202. doi: 10.1089/ten.TEB.2011.0365. Epub 2011 Dec 28.
Enamel matrix derivative (EMD), the active component of Emdogain®, is a viable option in the treatment of periodontal disease owing to its ability to regenerate lost tissue. It is believed to mimic odontogenesis, though the details of its functioning remain the focus of current research.
The aim of this article is to review all relevant literature reporting on the composition/characterization of EMD as well as the effects of EMD, and its components amelogenin and ameloblastin, on the behavior of various cell types in vitro. In this way, insight into the underlying mechanism of regeneration will be garnered and utilized to propose a model for the molecular arrangement and functioning of EMD.
A review of in vitro studies of EMD, or components of EMD, was performed using key words "enamel matrix proteins" OR "EMD" OR "Emdogain" OR "amelogenin" OR "ameloblastin" OR "sheath proteins" AND "cells." Results of this analysis, together with current knowledge on the molecular composition of EMD and the structure and regulation of its components, are then used to present a model of EMD functioning.
Characterization of the molecular composition of EMD confirmed that amelogenin proteins, including their enzymatically cleaved and alternatively spliced fragments, dominate the protein complex (>90%). A small presence of ameloblastin has also been reported. Analysis of the effects of EMD indicated that gene expression, protein production, proliferation, and differentiation of various cell types are affected and often enhanced by EMD, particularly for periodontal ligament and osteoblastic cell types. EMD also stimulated angiogenesis. In contrast, EMD had a cytostatic effect on epithelial cells. Full-length amelogenin elicited similar effects to EMD, though to a lesser extent. Both the leucine-rich amelogenin peptide and the ameloblastin peptides demonstrated osteogenic effects. A model for molecular structure and functioning of EMD involving nanosphere formation, aggregation, and dissolution is presented.
EMD elicits a regenerative response in periodontal tissues that is only partly replicated by amelogenin or ameloblastin components. A synergistic effect among the various proteins and with the cells, as well as a temporal effect, may prove important aspects of the EMD response in vivo.
釉基质衍生物（EMD）是 Emdogain®的有效成分，由于其能够再生丢失的组织，因此是治疗牙周病的可行选择。它被认为可以模拟牙发生，但其作用的细节仍是当前研究的重点。
本文旨在综述所有有关 EMD 的组成/特征以及 EMD 及其成分釉原蛋白和釉基质蛋白对各种细胞类型体外行为的影响的文献。通过这种方式，可以深入了解再生的潜在机制，并利用该机制提出 EMD 分子排列和功能的模型。
使用关键词“牙釉质基质蛋白”或“EMD”或“Emdogain”或“釉原蛋白”或“釉基质蛋白”或“鞘蛋白”和“细胞”，对 EMD 或其成分的体外研究进行综述。然后，将该分析的结果与当前关于 EMD 的分子组成以及其成分的结构和调节的知识结合起来，提出 EMD 作用的模型。
对 EMD 分子组成的特征描述证实，釉原蛋白（包括其酶切和选择性剪接片段）占蛋白质复合物的主导地位（>90%）。也有报道称少量存在釉基质蛋白。对 EMD 作用的分析表明，各种细胞类型的基因表达、蛋白产生、增殖和分化受到 EMD 的影响，通常被增强，特别是对牙周韧带和成骨细胞类型。EMD 还刺激了血管生成。相比之下，EMD 对上皮细胞具有细胞抑制作用。全长釉原蛋白引起与 EMD 相似的作用，但程度较轻。富含亮氨酸的釉原蛋白肽和釉基质蛋白肽都具有成骨作用。提出了一个涉及纳米球形成、聚集和溶解的 EMD 分子结构和功能的模型。
EMD 在牙周组织中引发再生反应，而仅部分由釉原蛋白或釉基质蛋白成分复制。各种蛋白质与细胞之间的协同作用以及时间效应可能是 EMD 在体内反应的重要方面。
